Hypnosis is an artificially induced altered state of consciousness, which resembles sleep. In anesthesia, the level of hypnosis is controlled by induction of sedative drugs or anesthetic agents. Hypnosis always refers to the suppression or alteration of the (cortical) brain functions. The depth of hypnosis can be clinically tested by non-noxious stimulation of the patient, such as loud speak or light squeeze, shake or touch, and by observing the patient responses, such as eye opening, communication ability, etc. Hypnotic drugs typically increase the overall inhibitory neuronal functions, as they usually affect the GABA (gamma-aminobutyric acid) system in the brain. Therefore, the hypnotics suppress both the cortical and subcortical activities in the brain. As a consequence, also the autonomic and reflex functions in the brain are altered and suppressed.
The depth of hypnosis is not directly measurable. Therefore, drug delivery systems have to derive the level of hypnosis from a surrogate signal or from indirectly measured parameters. The most common and popular surrogate signal for this purpose is the EEG, from which several parameters may be determined. During the past few years, some commercial validated devices for measuring the level of hypnosis in clinical set-up during anesthesia or sedation have become available. Such devices, which are based on a processed EEG signal and examine the signal as a whole with its multiple features, are marketed, for example, by GE Healthcare Finland Oy, Kuortaneenkatu 2, FIN-00510 Helsinki (Entropy Index) and by Aspect Medical Systems, Inc., 141 Needham Street, Newton, Mass. 02464, U.S.A. (Bispectral Index, BIS™).
In particular situations, the relation between the measured hypnotic level of the patient and the hypnotic drug concentration in the brain may be abnormal. For example, if severe bleeding, a stroke, or cardiac arrest takes place, the level of hypnosis is no longer controlled only by the hypnotic drug but also by the oxygenation of the brain. Certain anesthetic agents, such as sevoflurane, tend to induce epileptic seizures, which affect the level of hypnosis and also have an effect on the EEG-based measurement. Due to an underlying illness, the patient may show an abnormal response to some of the administered drugs. In these situations, interpretation of the measurement requires particular expertise.
Another issue aggravating the assessment of the level of hypnosis is that the EEG signals to be measured are weak, of the order of a few hundred microvolts, which makes them vulnerable to both external interferences caused by surrounding equipment and internal interferences caused by patient's eye or body movements and/or interfering EMG or ECG signal components, for example. With regard to the external interferences, an operation room is an especially demanding environment, since it is equipped with a plurality of devices that may act as interference sources from the point of view of the assessment of the level of hypnosis. Modern artifact detection methods have helped to minimize the problem but not completely solved it.
It has also been suggested that the administration of a hypnotic drug could be controlled in a closed loop fashion. U.S. Pat. No. 6,631,291 B2 discloses a system in which a quantification of the complexity of the EEG signal data measured from the patient is used to determine the patient's hypnotic level and to control the administration of a hypnotic drug to the patient in a closed loop fashion. A closed loop drug administration system generally refers to a system in which the administration is controlled automatically based on feedback measurement data measured from the patient, whereas an open loop drug administration system refers to a system in which such feedback measurement data is not automatically utilized for the control of drug administration.
Furthermore, U.S. Patent Application 2006/0217628 discloses a closed loop system in which an index of hypnosis and an index of nociception are measured from the patient and supplied to a control unit. The control unit determines the location of patient state on a two-dimensional plot. The control unit further compares the determined location with the input parameters defining the targeted location and controls the anesthetic delivery system to shift the state towards the targeted state or to maintain the state of the patient in the targeted domain.
Due to the above-mentioned difficulties in recognizing all factors possibly disturbing the measurement of the level of hypnosis, the performance of the present-day measurement systems is compromised in presence of anomalies, i.e. in situations in which the logical relation between the measured hypnotic level and the drug effect in the brain is altered due to an abnormal reason. As discussed above, the anomalies may be of medical origin or caused by unwanted electrical signals (interference in the measurement).
The above-mentioned difficulty in recognizing all disturbing factors also complicates the design of a closed loop drug administration system. In anomalous situations the control system would often lack the pieces of information that would be necessary for the correct interpretation of the situation and for correct decisions regarding drug administration.